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Updated: Jan 20, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Improving the anticancer effect of afatinib and microRNA by using lipid polymeric nanoparticles conjugated with dual
Shu-Ting Hong1, Huaching Lin2, Chen-Shen Wang1
1Institute of Pharmacology, National Yang-Ming University, Taipei, 112, Taiwan.
Background:
The emergence of resistance to chemotherapy or target therapy, tumor metastasis, and systemic toxicity caused by available anticancer drugs hamper the successful colorectal cancer (CRC) treatment. The rise in epidermal growth factor receptor (EGFR; human epidermal growth factor receptor 1; HER1) expression and enhanced phosphorylation of HER2 and HER3 are associated with tumor resistance, metastasis and invasion, thus resulting in poor outcome of anti-CRC therapy. The use of afatinib, a pan-HER inhibitor, is a potential therapeutic approach for resistant CRC. Additionally, miR-139 has been reported to be negatively correlated with chemoresistance, metastasis, and epithelial-mesenchymal transition (EMT) of CRC. Hence, we develop a nanoparticle formulation consisting of a polymer core to carry afatinib or miR-139, which is surrounded by lipids modified with a targeting ligand and a pH-sensitive penetrating peptide to improve the anticancer effect of cargos against CRC cells.
Results:
Our findings show that this formulation displays a spherical shape with core/shell structure, homogeneous particle size distribution and negative zeta potential. The prepared formulations demonstrate a pH-sensitive release profile and an enhanced uptake of cargos into human colorectal adenocarcinoma Caco-2 cells in response to the acidic pH. This nanoparticle formulation incorporating afatinib and miR-139 exhibits low toxicity to normal cells but shows a better inhibitory effect on Caco-2 cells than other formulations. Moreover, the encapsulation of afatinib and miR-139 in peptide-modified nanoparticles remarkably induces apoptosis and inhibits migration and resistance of Caco-2 cells via suppression of pan-HER tyrosine kinase/multidrug resistance/metastasis pathways.
Conclusion:
This study proposes a multifunctional nanoparticle formulation for targeted modulation of apoptosis/EGFR/HER/EMT/resistance/progression pathways to increase the sensitivity of colon cancer cells to afatinib.
Insights
This study developed novel nanoparticles carrying afatinib and miR-139 to overcome colorectal cancer resistance. The formulation effectively targets cancer cells, reduces toxicity, and inhibits tumor progression by modulating key pathways.
Area of Science:
- Nanotechnology
- Oncology
- Biomedical Engineering
Background:
- Colorectal cancer (CRC) treatment is hindered by drug resistance, metastasis, and toxicity.
- Increased epidermal growth factor receptor (EGFR) signaling correlates with CRC progression and poor outcomes.
- Afatinib (a pan-HER inhibitor) and miR-139 show potential against resistant CRC and metastasis.
Purpose of the Study:
- To develop a targeted nanoparticle formulation for enhanced delivery of afatinib and miR-139 in CRC.
- To evaluate the efficacy of the nanoparticle formulation in overcoming chemoresistance and metastasis in CRC cells.
Main Methods:
- A core/shell nanoparticle system encapsulating afatinib and miR-139 was engineered.
- Lipid modification with a targeting ligand and pH-sensitive peptide for enhanced cellular uptake.
- In vitro assessment of nanoparticle characteristics, drug release, cellular uptake, toxicity, and anti-cancer effects on Caco-2 cells.
Main Results:
- The nanoparticles exhibited a spherical core/shell structure with pH-sensitive release and enhanced uptake in acidic tumor environments.
- The afatinib and miR-139 loaded nanoparticles demonstrated low toxicity to normal cells but potent inhibition of Caco-2 cells.
- Apoptosis was induced, and migration/resistance was inhibited by suppressing pan-HER tyrosine kinase, multidrug resistance, and metastasis pathways.
Conclusions:
- A multifunctional nanoparticle formulation effectively targets CRC cells and modulates critical cancer pathways.
- This approach enhances colon cancer cell sensitivity to afatinib, offering a promising strategy against resistant CRC.
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